Hydrochloric Acid → 2-(6-Fluoroquinolin-7-yl)acetic acid

HRID 2097954Notes

Reaction equation

HRID 2097954 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([CH2:8][C:9]([O:11]CC)=[O:10])[CH:7]=1.O[CH2:16][CH:17]([CH2:19]O)O.[N+]([C:24]1[CH:29]=CC=C[CH:25]=1)([O-])=O.S(=O)(=O)(O)O.Cl>C(O)C.[OH-].[Na+]>[F:14][C:5]1[C:6]([CH2:8][C:9]([OH:11])=[O:10])=[C:7]2[C:2](=[CH:3][CH:4]=1)[N:1]=[CH:19][CH:17]=[CH:16]2.[F:14][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][C:6]=1[CH2:8][C:9]([OH:11])=[O:10])[N:1]=[CH:29][CH:24]=[CH:25]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 753GlycerolHCID 1118Sulfuric AcidHCID 7416NitrobenzeneHCID 68759574Ethyl 2-(5-amino-2-fluorophenyl)acetate

Product 2

HCID 687556782-(6-Fluoroquinolin-5-yl)acetic acidHCID 687557882-(6-Fluoroquinolin-7-yl)acetic acidYield 88.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of ethyl 2-(5-amino-2-fluorophenyl)acetate (3.7 g, 18.8 mmol), glycerol (6.92 g, 75.2 mmol), nitrobenzene (4.63 g, 37.6 mmol) and ferrous sulfate (1.06 g, 3.76 mmol) was added conc. sulfuric acid (4.5 mL) dropwise. The reaction mixture was heated at 120° C. for 15 hr. After cooled to RT, the reaction mixture was diluted with ethanol (20 mL), and 2N aq. NaOH was introduced to adjust pH about 13. The resulting mixture was stirred at RT for 1 hr. Then the reaction was neutralized with aq. HCl and filtered, and the dark brown precipitate was washed with methanol. The combined filtrate was concentrated to dryness in vacuum. The resulting residue was washed adequately with methanol and the combined filtrate was concentrated to dryness to give crude product, which was isolated by flash column chromatography to give 2-(6-fluoroquinolin-5-yl)acetic acid and 2-(6-fluoroquinolin-7-yl)acetic acid (1.7 g, 44%). LC-MS (0.05% TFA): [M+1]+ 206.1. 1H-NMR (DMSO-d6, 400 MHz): δ 12.66 (brs, 1H), 8.90 (m, 1H), 8.35 (m, 1H), 8.04 (m, 1H), 7.76 (m, 1H), 7.56 (m, 1H), 3.88 (s, 2H).

Workup

  1. temperatureAfter cooled to RT
  2. additionwas introduced
  3. filtrationfiltered
  4. washthe dark brown precipitate was washed with methanol
  5. concentrationThe combined filtrate was concentrated to dryness in vacuum
  6. washThe resulting residue was washed adequately with methanol
  7. concentrationthe combined filtrate was concentrated to dryness
  8. customto give crude product
  9. customwhich was isolated by flash column chromatography

Sources & evidence

ORD record
ord-88b3a4cc25b64503ab3d3224d06a7ca9
Source dataset
uspto-grants-2013_05
Patent number
US08450363B2

Reaction notes

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